Modified bare-back micro-retrograde tibial arterial access to facilitate peripheral endovascular therapy.

Patients with critical limb threatening ischemia often present with complex segmental peripheral arterial chronic total occlusions, which might not be amenable to traditional antegrade revascularization techniques. For these patients, alternative retrograde revascularization techniques could be necessary. In the present report, we describe a novel modified retrograde cannulation technique using a bare back technique that eliminates the need for conventional tibial access sheath placement and, instead, facilitates distal arterial blood sampling, blood pressure monitoring, retrograde administration of contrast agents and vasoactive substances, and a rapid-exchange strategy. This cannulation strategy can serve as part of the armamentarium in the treatment of patients with complex peripheral arterial occlusions.

Chronic anti-coagulation therapy reduced mortality in patients with high cardiovascular risk early in COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviating these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients hospitalized during the early phase of the pandemic in the United States. METHODS: A retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous outpatient therapeutic AC for a least 90 days prior to their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR). RESULTS: We identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events. CONCLUSION: AC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus.

Chronic Anti-Coagulation Therapy Reduced Mortality In Patients With High Cardiovascular Risk Early In COVID-19 Pandemic.

Background: Coronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviate these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients during the early phase of the pandemic in the United States. Methods: A retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous therapeutic AC for a least 30 days prior to or after their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR). Results: We identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events. Conclusion: AC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus.

Reoperative Brachial Plexus Neurolysis After Previous Anatomically Complete Supraclavicular Decompression for Neurogenic Thoracic Outlet Syndrome: A 10-Year Single-Center Case Series.

BACKGROUND: Optimal management of recurrent neurogenic thoracic outlet syndrome (NTOS) remains a considerable challenge. OBJECTIVE: To assess the safety and effectiveness of reoperative brachial plexus neurolysis in patients with recurrent NTOS. METHODS: From 2009 to 2019, 85 patients underwent reoperative supraclavicular brachial plexus neurolysis for recurrent NTOS after a previous anatomically complete supraclavicular decompression. Data from a prospectively maintained database were analyzed retrospectively. RESULTS: The mean patient age at reoperation was 36.9 ± 1.3 (range 15-64) years, 75% were female, and the interval after previous primary operation was 2.5 ± 0.2 years. Intervening injury had precipitated recurrent NTOS in 14 patients (16%), and the mean Disability of the Arm, Shoulder, and Hand (QuickDASH) score before reoperation was 65.2 ± 2.6, reflecting substantial disability. Operative findings consisted of dense fibrous scar tissue surrounding/encasing the brachial plexus. Compared with the previous primary operations, reoperations had a shorter operative time (198 ± 4 vs 161 ± 5 minutes, P < .01) and hospital stay (4.4 ± 0.2 vs 3.6 ± 0.1 days, P < .01), but there were no significant differences in the frequency of prolonged hospitalization (7.1% vs 4.7%), early reoperation (3.5% vs 1.2%), or 30-day hospital readmission (8.2% vs 7.1%). During a median follow-up of 4.8 years, QuickDASH scores improved by 23.3 ± 2.6 (34.2% ± 3.6%; P < .01) and patient-rated outcomes were excellent in 24%, good in 42%, fair in 26%, and poor in 8%. CONCLUSION: Reoperative supraclavicular brachial plexus neurolysis is technically challenging but safe and effective treatment for recurrent NTOS, with significant improvements in symptoms and function. Diminishing perineural scar tissue development and avoiding secondary injury would likely decrease the need for reoperations.

Anatomic characteristics associated with superior mesenteric artery stent graft placement during fenestrated para/suprarenal aneurysm repair.

OBJECTIVE: According to the instructions for use, fenestrated endovascular aortic aneurysm repair (FEVAR) with the Zenith fenestrated endograft (ZFEN; Cook Medical, Bloomington, Ind) requires ≥4 mm of nonaneurysmal infrarenal neck length, and superior mesenteric artery (SMA) stenting is optional. In the present study, we evaluated the outcomes of FEVAR with SMA stent grafting relative to SMA scallops or unstented fenestrations and their anatomic differences. METHODS: We performed a single-institution retrospective analysis of patients who had undergone FEVAR with an SMA scallop or large fenestration with and without SMA stent grafting from June 2012 to May 2020 after institutional review board approval. RESULTS: Of the 203 aneurysms repaired with ZFENs, 127 were included in our analysis. Of these 127 aneurysms, 55 had stent grafted SMA fenestrations, 38 unstented SMA fenestrations, and 34 SMA scallops. Technical success was achieved in all patients. The operative times were longer (335.5 ± 16.4 minutes vs 265.0 ± 12.8 minutes vs 269.0 ± 12.7 minutes; P < .001) and the transfusion rates were higher (33% vs 8% vs 18%; P = .01) in the SMA stent graft group. However, the fluoroscopy time (65.4 ± 3.76 minutes vs 58.3 ± 3.94 minutes vs 51.4 ± 4.75 minutes; P = .05) and contrast volume (92.2 ± 5.17 mL vs 87.1 ± 6.73 mL vs 93.1 ± 5.89 mL; P = .84) were not significantly different. Anatomically, the patients who had undergone FEVAR with a ZFEN and SMA stent grafting had had shorter infrarenal neck (1.73 ± 1.18 mm vs 4.92 ± 1.16 mm vs 6.28 ± 1.42 mm; P = .03) and infra-SMA neck (10.3 ± 1.39 mm vs 23.9 ± 1.24 mm vs 26.8 ± 1.67 mm; P < .001) lengths. In the SMA stent graft group, one patient had developed small bowel necrosis after embolization of an intraoperatively perforated jejunal branch and two had developed colonic ischemia of unclear etiology with patent SMA stent grafts found on imaging. Endograft migration and SMA occlusion with bowel ischemia occurred in one patient in the SMA fenestration group. Overall mortality (24% vs 21% vs 18%; P = .82) and 30-day mortality (5% vs 3% vs 3%; P = .80) were comparable between the three groups. In addition, the incidence of type III endoleak (5% vs 3% vs 3%; P = .45) and the need for reintervention (20% vs 18% vs 12%; P = .60) were similar across all three groups. The mean follow-up duration was longer for the SMA scallop group, which can be attributed to 82% of these occurring in the first one half of the study period. CONCLUSIONS: Despite the added technical complexity, SMA stenting enabled FEVAR in patients with pararenal and suprarenal aneurysms with high rates of technical success and no increased risk of mortality, major adverse events, type III endoleaks, or reintervention.

Anatomically Complete Supraclavicular Reoperation for Recurrent Neurogenic Thoracic Outlet Syndrome: Clinical Characteristics, Operative Findings, and Long-term Outcomes.

BACKGROUND: The clinical outcomes of reoperations for recurrent neurogenic thoracic outlet syndrome (NTOS) remain undefined. METHODS: From 2009 to 2019, 90 patients with recurrent NTOS underwent anatomically complete supraclavicular reoperation after previous operation(s) performed at other institutions using either supraclavicular (Prev-SC = 48), transaxillary (Prev-TA = 31), or multiple/combination (Prev-MC = 11) approaches. Prospectively maintained data were analyzed retrospectively. RESULTS: The mean patient age was 39.9 ± 1.4 years, 72% were female, and the mean interval after previous operation was 4.1 ± 0.6 years. The mean Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score was 62 ± 2, reflecting substantial preoperative disability. Residual scalene muscle was present in 100% Prev-TA, 79% Prev-SC, and 55% Prev-MC (P < .05). Retained/residual first rib was present in 90% Prev-TA, 75% Prev-SC, and 55% Prev-MC (P < .05). There were no differences in operative time (overall 210 ± 5 minutes), length of hospital stay (4.7 ± 0.2 days), or 30-day readmissions (7%). During follow-up of 5.6 ± 0.3 years, the improvement in QuickDASH scores was 21 ± 2 (36% ± 3%) (P < .01) and patient-rated outcomes were excellent in 10%, good in 36%, fair in 43%, and poor in 11%. CONCLUSIONS: Anatomically complete decompression for recurrent NTOS can be safely and effectively accomplished by supraclavicular reoperation, regardless of the type of previous operation. Residual scalene muscle and retained/residual first rib are more frequently encountered after transaxillary operations than after supraclavicular or multiple/combined operations. Supraclavicular reoperation can achieve significant symptom reduction and functional improvement for approximately 90% of patients with recurrent NTOS.

Outcomes of Orbital Atherectomy in Patients with Critical Limb Threatening Ischemia and Diabetes.

Purpose: Patients with diabetes and critical limb threatening ischemia (CLTI) are at significantly higher risk of limb loss and death. Here we evaluate the outcomes of orbital atherectomy (OA) for treatment of CLTI in patients with and without diabetes. Methods: Retrospective analysis of the LIBERTY 360 study was performed to evaluate baseline demographics, and peri-procedural outcomes between patients with CLTI, and with and without diabetes. Hazard ratios (HRs) were determined with Cox regression to examine the impact of OA in patients with diabetes and CLTI over a 3-year follow-up. Results: A total of 289 patients (201 with diabetes, 88 without diabetes) with Rutherford classification 4-6 were included. Patients with diabetes had higher proportion of renal disease (48.3% vs 28.4%, p=0.002), prior minor/major limb amputation (26% vs 8%, p<0.005), and presence of wounds (63.2% vs 48.9%, p=0.027). Operative times, radiation dosage, and contrast volume were similar between groups. The rate of distal embolization was higher in patients with diabetes (7.8% vs 1.9%, p=0.01; OR 4.33 [0.99, 18.88], p=0.05). However, at 3-years post-procedure, patients with diabetes had no differences in freedom from target vessel/lesion revascularization (HR 1.09, p=0.73), major adverse events (MAE; HR 1.25, p=0.36), major target limb amputation (HR 1.74, p=0.39), and death (HR 1.11, p=0.72). Conclusion: The LIBERTY 360 observed high limb preservation and low MAEs in patients with diabetes and CLTI. Higher distal embolization was observed with OA in patients with diabetes, but OR did not indicate a significant difference in risk between groups.

Management of Seat Belt-type Blunt Abdominal Aortic Trauma and Associated Injuries in Pediatric Patients.

BACKGROUND: "Seat belt-type" pediatric abdominal aortic trauma is uncommon but potentially lethal. During high speed motor vehicle collisions (MVCs), seat or lap belt restraints may concentrate forces in a band-like pattern across the abdomen, resulting in the triad of hollow viscus perforation, spine fracture, and aortoiliac injury. We report 4 cases of pediatric seat belt-type aortic trauma and review management strategies for the aortic disruption and the associated constellation of injuries. METHODS: -approved, retrospective review of all pediatric patients requiring surgical intervention for seat belt-type constellation of abdominal aortic/iliac and associated injuries over a 5-year period. Blunt thoracic aortic injuries were excluded. RESULTS: We identified 4 patients, ranging from 2 to 17 years of age, who required surgical correction of seat belt-type aortoiliac trauma and associated injuries: 3 abdominal aortas and 1 left common iliac artery. The majority (3/4 patients) were hemodynamically unstable at emergency room presentation, and all underwent computed tomography angiography of the chest/abdomen/pelvis during initial resuscitation. Injuries of the suprarenal and proximal infrarenal aorta were accompanied by unilateral renal artery avulsion requiring nephrectomy. Presumed or proven spinal instability mandated supine positioning and midline laparotomy, with medial visceral rotation utilized for proximal injuries. Aortoiliac injuries requiring repair were accompanied by significant distal intraluminal prolapse of dissected intima, with varying degrees of obstruction. Conduit selection was dictated by the presence of enteric contamination and the rapid availability of an autologous conduit. The sole neurologic deficit was irreparable at presentation. CONCLUSIONS: Seat belt aortoiliac injuries in pediatric patients require prompt multidisciplinary evaluation. Evidence of contained aortoiliac transection, major branch vessel avulsion, and bowel perforation mandates immediate exploration, which generally precedes spinal interventions. Lesser degrees of aortoiliac injuries have been managed with surveillance, but long-term follow-up is needed to fully validate this approach.

Racial/ethnic differences in necrotizing enterocolitis incidence and outcomes in premature very low birth weight infants.

BACKGROUND: As advances in neonatal intensive care increase the survival of extremely premature infants, the at-risk population for necrotizing enterocolitis (NEC) continues to rise. Although racial health disparities in preterm births have been well documented, large-scale studies exploring racial differences in NEC outcomes are lacking. Here, we conduct a study of racial health disparities in NEC using a nationally representative multicenter cohort. STUDY DESIGN: Infants ≤1500 g birth weight and ≤30 weeks gestational age admitted in the first week after birth to neonatal intensive care units in the Pediatrix Medical group from 1997 to 2015 were included. Multivariable logistic regression was used to determine the adjusted odds ratio (AOR) of risk factors related to NEC and associated mortality. RESULTS: Of the 126,089 (45% non-Hispanic White, 27% non-Hispanic Black, and 19% Hispanic) infants who met the inclusion criteria, 8796 (7%) developed NEC. On multivariable analysis, non-Hispanic Black and Hispanic infants had higher odds of developing NEC (AOR 1.31, 95% confidence interval (CI) [1.24-1.39], p < 0.001 and AOR 1.30 [1.21-1.39], p < 0.001, respectively). Among infants with NEC, mortality was higher in non-Hispanic Black and Hispanic infants compared to non-Hispanic White infants (AOR 1.35 [1.15-1.58], p < 0.001 and AOR 1.31 [1.09-1.56], p = 0.003, respectively). CONCLUSION: Our study demonstrates that non-Hispanic Black and Hispanic infants are significantly more likely to be diagnosed with NEC. In addition, non-Hispanic Black and Hispanic infants have higher odds of death after NEC compared to non-Hispanic White infants. Further studies are necessary to investigate the etiology of these health disparities and to test interventions to improve these health outcomes.

Transplantation of human skin microbiota in models of atopic dermatitis.

Atopic dermatitis (AD) is characterized by reduced barrier function, reduced innate immune activation, and susceptibility to Staphylococcus aureus. Host susceptibility factors are suggested by monogenic disorders associated with AD-like phenotypes and can be medically modulated. S. aureus contributes to AD pathogenesis and can be mitigated by antibiotics and bleach baths. Recent work has revealed that the skin microbiome differs significantly between healthy controls and patients with AD, including decreased Gram-negative bacteria in AD. However, little is known about the potential therapeutic benefit of microbiome modulation. To evaluate whether parameters of AD pathogenesis are altered after exposure to different culturable Gram-negative bacteria (CGN) collected from human skin, CGN were collected from healthy controls and patients with AD. Then, effects on cellular and culture-based models of immune, epithelial, and bacterial function were evaluated. Representative strains were evaluated in the MC903 mouse model of AD. We found that CGN taken from healthy volunteers but not from patients with AD were associated with enhanced barrier function, innate immunity activation, and control of S. aureus. Treatment with CGN from healthy controls improved outcomes in a mouse model of AD. These findings suggest that a live-biotherapeutic approach may hold promise for treatment of patients with AD.

Strain Specific Phage Treatment for Staphylococcus aureus Infection Is Influenced by Host Immunity and Site of Infection.

The response to multi-drug resistant bacterial infections must be a global priority. While mounting resistance threatens to create what the World Health Organization has termed a "post-antibiotic era", the recent discovery that antibiotic use may adversely impact the microbiome adds further urgency to the need for new developmental approaches for anti-pathogen treatments. Methicillin-resistant Staphylococcus aureus (MRSA), in particular, has declared itself a serious threat within the United States and abroad. A potential solution to the problem of antibiotic resistance may not entail looking to the future for completely novel treatments, but instead looking into our history of bacteriophage therapy. This study aimed to test the efficacy, safety, and commercial viability of the use of phages to treat Staphylococcus aureus infections using the commercially available phage SATA-8505. We found that SATA-8505 effectively controls S. aureus growth and reduces bacterial viability both in vitro and in a skin infection mouse model. However, this killing effect was not observed when phage was cultured in the presence of human whole blood. SATA-8505 did not induce inflammatory responses in peripheral blood mononuclear cultures. However, phage did induce IFN gamma production in primary human keratinocyte cultures and induced inflammatory responses in our mouse models, particularly in a mouse model of chronic granulomatous disease. Our findings support the potential efficacy of phage therapy, although regulatory and market factors may limit its wider investigation and use.

Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing.

Radiation therapy (RT) is used for local tumor control through direct killing of tumor cells. Radiation-induced cell death can trigger tumor antigen-specific immune responses, but these are often noncurative. Radiation has been demonstrated to induce immunogenic modulation (IM) in various tumor types by altering the biology of surviving cells to render them more susceptible to T cell-mediated killing. Little is known about the mechanism(s) underlying IM elicited by sub-lethal radiation dosing. We have examined the molecular and immunogenic consequences of radiation exposure in breast, lung, and prostate human carcinoma cells. Radiation induced secretion of ATP and HMGB1 in both dying and surviving tumor cells. In vitro and in vivo tumor irradiation induced significant upregulation of multiple components of the antigen-processing machinery and calreticulin cell-surface expression. Augmented CTL lysis specific for several tumor-associated antigens was largely dictated by the presence of calreticulin on the surface of tumor cells and constituted an adaptive response to endoplasmic reticulum stress, mediated by activation of the unfolded protein response. This study provides evidence that radiation induces a continuum of immunogenic alterations in tumor biology, from immunogenic modulation to immunogenic cell death. We also expand the concept of immunogenic modulation, where surviving tumor cells recovering from radiation-induced endoplasmic reticulum stress become more sensitive to CTL killing. These observations offer a rationale for the combined use of radiation with immunotherapy, including for patients failing RT alone.

Cancer vaccines targeting carcinoembryonic antigen: state-of-the-art and future promise.

Concurrent with the US FDA's approval of the first therapeutic cancer vaccine, and supported by mounting clinical evidence indicating that targeting carcinoembryonic antigen (CEA) can safely overcome pre-existing tolerance, a multitude of novel CEA cancer vaccines are now in various stages of development. Since cancer-driven immune suppression often limits the efficacy of vaccines, numerous strategies are being examined in both preclinical and clinical settings to overcome immunosuppressive elements, including the combined use of vaccines with certain chemotherapies, immune checkpoint inhibitors, small-molecule targeted therapies and radiation. This review discusses the current state and future direction of therapeutic cancer vaccines targeting CEA, based on advances achieved over the last 5 years.